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2oqp

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Revision as of 10:49, 23 January 2008 by OCA (Talk | contribs)
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2oqp

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Solution structure of human interleukin-21

Overview

The high resolution three-dimensional structure of human interleukin, (hIL)-21 has been resolved by heteronuclear NMR spectroscopy. Overall, the, hIL-21 structure is dominated by a well defined central four-helical, bundle, arranged in an up-up-down-down topology, as observed for other, cytokines. A segment of the hIL-21 molecule that includes the third, helical segment, helix C, is observed to exist in two distinct and, interchangeable states. In one conformer, the helix C segment is presented, in a regular, alpha-helical conformation, whereas in the other conformer, this segment is largely disordered. A structure-based sequence alignment, of hIL-21 with receptor complexes of the related cytokines, interleukin-2, and -4, implied that this particular segment is involved in receptor, binding. An hIL-21 analog was designed to stabilize the region around, helix C through the introduction of a segment grafted from hIL-4. This, novel hIL-21 analog was demonstrated to exhibit a 10-fold increase in, potency in a cellular assay.

About this Structure

2OQP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue., Bondensgaard K, Breinholt J, Madsen D, Omkvist DH, Kang L, Worsaae A, Becker P, Schiodt CB, Hjorth SA, J Biol Chem. 2007 Aug 10;282(32):23326-36. Epub 2007 Jun 12. PMID:17565991

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